The long-term objectives of the research we propose to perform under this career development award are to reduce the cost and to increase the speed and accuracy of DNA sequencing. The research will be performed in the Laboratory facilities of the Stanford Yeast Genome Project and the Center for Advanced Medical Informatics at Stanford. The specific aims of the proposed work are: 1. to provide training to the candidate in genetics, molecular biology, and laboratory methods relevant to the Human Genome Project, by means of formal courses and laboratory rotations, 2. to improve the accuracy of base-calling software used for DNA sequencing, by applying new statistical methods, 3. to provide more accurate estimates of the probability of error in base calling, and 4. to develop programs that will automatically determine the sequence- dependent mobility and intensity effects of new chemistries and procedures used for DNA sequence gel electrophoresis. With these programs, we will be able to evaluate new sequencing procedures more quickly than is currently possible.